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1.
M Shadidy X Caubit R Olsen O M Seternes U Moens S Krauss 《Biochimica et biophysica acta》1999,1446(3):295-307
We have identified mouse and human FKBP60, a new member of the FKBP gene family. FKBP60 shares strongest homology with FKBP65 and SMAP. FKBP60 contains a hydrophobic signal peptide at the N-terminus, 4 peptidyl-prolyl cis/trans isomerase (PPIase) domains and an endoplasmic reticulum retention motif (HDEL) at the C-terminus. Immunodetection of HA-tagged FKBP60 in NIH-3T3 cells suggests that FKBP60 is segregated to the endoplasmic reticulum. Northern blot analysis shows that FKBP60 is predominantly expressed in heart, skeletal muscle, lung, liver and kidney. With N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as a substrate, recombinant GST-FKBP60 is shown to accelerate effectively the isomerization of the peptidyl-prolyl bond. This isomerization activity is inhibited by FK506. mFKBP60 binds Ca2+ in vitro, presumably by its C-terminal EF-hand Ca2+ binding motif, and is phosphorylated in vivo. hFKBP60 has been mapped to 7p12 and/or 7p14 by fluorescence in situ hybridization (FISH). 相似文献
2.
Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH1-34) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH1-34 has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction
osteogenesis. These studies have demonstrated that intermittent PTH1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal
stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH1-34 has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced
bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH1-34 treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH1-34 treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing
in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the
appropriate patient population for PTH1-34 therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications)
and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering. 相似文献
3.
E Estébanez-Perpi?á A Bayés J Vendrell M A Jongsma D P Bown J A Gatehouse R Huber W Bode F X Avilés D Reverter 《Journal of molecular biology》2001,313(3):629-638
The cotton bollworm Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) is one of the most serious insect pests in Australia, India and China. The larva causes substantial economical losses to legume, fibre, cereal oilseed and vegetable crops. This pest has proven to be difficult to control by conventional means, mainly due to the development of pesticide resistance. We present here the 2.5 A crystal structure from the novel procarboxypeptidase (PCPAHa) found in the gut extracts from H. armigera larvae, the first one reported for an insect. This metalloprotease is synthesized as a zymogen of 46.6 kDa which, upon in vitro activation with Lys-C endoproteinase, yields a pro-segment of 91 residues and an active carboxypeptidase moiety of 318 residues. Both regions show a three-dimensional structure quite similar to the corresponding structures in mammalian digestive carboxypeptidases, the most relevant structural differences being located in the loops between conserved secondary structure elements, including the primary activation site. This activation site contains the motif (Ala)(5)Lys at the C terminus of the helix connecting the pro- and the carboxypeptidase domains. A remarkable feature of PCPAHa is the occurrence of the same (Ala)(6)Lys near the C terminus of the active enzyme. The presence of Ser255 in PCPAHa instead of Ile and Asp found in the pancreatic A and B forms, respectively, enlarges the S1' specificity pocket and influences the substrate preferences of the enzyme. The C-terminal tail of the leech carboxypeptidase inhibitor has been modelled into the PCPAHa active site to explore the substrate preferences and the enzymatic mechanism of this enzyme. 相似文献
4.
I. N. Semenchuk L. A. Taranova A. A. Kalenyuk P. V. Il’yasov A. N. Reshetilov 《Applied Biochemistry and Microbiology》2000,36(1):69-72
The operating and storage stability of a receptor element of an amperometric biosensor based on thePseudomonas rathonis strain T capable of degrading surfactants was tested. Microbial cells were immobilized by incorporation in gels (agar, agarose,
and calcium-alginate), polyvinyl alcohol membrane, adhesion to Chromatographic paper GF/A, or by cross-linking induced by
glutaric aldehyde. Incorporation of microbial cells in agar gel provides long-standing conservation of their activity and
viability during measurements of high concentrations of surfactants and allows the receptor element of the biosensor to be
rapidly recovered after measurements. 相似文献
5.
S. I. Tkachenko A. R. Mingaleev V. M. Romanova A. E. Ter-Oganes’yan T. A. Shelkovenko S. A. Pikuz 《Plasma Physics Reports》2009,35(9):734-753
Distribution of matter in the discharge channel formed upon a nanosecond electrical explosion of a single wire in air and
vacuum was studied experimentally. Simultaneous use of optical, UV, and X-ray diagnostics made it possible to distinguish
qualitatively different regions of the discharge channel, such as the current-carrying layers and the region occupied by a
weakly conducting cold plasma. Several series of experiments with 25-μm-diameter 12-mm-long wires made of different materials
were performed. The charging voltage and the current amplitude were varied in the ranges of U
0 = 10–20 kV and I
max ∼ 5–10 kA, respectively. Explosion regimes with a current pause and with and without current interruption, as well as with
wire preheating in air and vacuum, were studied. Shadow and schlieren images of the discharge channel were obtained using
optical probing at the second harmonic of a YAG: Nd+3 laser (λ = 0.532 μm, τ ∼ 10 ns). In the experiments carried out in vacuum, X-ray images of the discharge channel were also
obtained using an X-pinch as a point source of probing radiation and UV images were recorded using a four-frame MCP camera. 相似文献
6.
The Asian Tree Toad genus Pedostibes, as currently understood, exhibits a conspicuously disjunct distribution, posing several immediate questions relating to the biogeography and taxonomy of this poorly known group. The type species, P. tuberculosus and P. kempi, are known only from India, whereas P. hosii, P. rugosus, and P. everetti are restricted to Southeast Asia. Several studies have shown that these allopatric groups are polyphyletic, with the Indian Pedostibes embedded within a primarily South Asian clade of toads, containing the genera Adenomus, Xanthophryne, and Duttaphrynus. Southeast Asian Pedostibes on the other hand, are nested within a Southeast Asian clade, which is the sister lineage to the Southeast Asian river toad genus Phrynoidis. We demonstrate that Indian and Southeast Asian Pedostibes are not only allopatric and polyphyletic, but also exhibit significant differences in morphology and reproductive mode, indicating that the Southeast Asian species’ are not congeneric with the true Pedostibes of India. As a taxonomic solution, we describe a new genus, Rentapia
gen. nov. to accommodate the Southeast Asian species. 相似文献
7.
A. V. Nikolayev Yu. V. Kirichek O. I. Ostrovskaya I. I. Maletina K. I. Petko L. M. Yagupol’skii 《Neurophysiology》1999,31(3):191-193
With the use of a patch-clamp technique in the whole-cell configuration, we studied the effects of pinacidil and its fluorine
derivatives on A-type potassium current (I
A) through the membrane of pyramidal neurons of the rat hippocampus. Hydrogen peroxide (10 mM) exerted no influence on the
rate of inactivation ofI
A; therefore, this current is probably mediated by Shal Kv4.2 potassium channels. Pinacidil demonstrated the properties of
a weakI
A blocker: in the 500 μM concentration it blocked about 45% of the current, while 50 μM of pinacidil fluorine derivatives were
capable of blocking up to 30% ofI
A. The effects of pinacidil and its derivatives showed no dependence on the stimulating potential. A similar pattern of the
effects of pinacidil fluorine derivatives, which are an order of magnitude stronger than those of pinacidil itself, allows
us to suppose that the imine nitrogen of the tested compounds is significantly more involved in the molecular interaction
with the site of an A-type potassium channel than the pyridine nitrogen. 相似文献
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